Signals from the brain can provide a new communication channel - a brain-computer interface (BCI) - for those with severe neuromuscular disorders such as amyotrophic lateral sclerosis, brainstem stroke, and spinal cord injury. BCI technology can allow people who are completely paralyzed, or "locked in," to express wishes to caregivers, use word processing programs, access the Internet, or even operate neuroprostheses. Up to now, BCI research has demonstrated that a variety of different methods using different brain signals, signal analyses, and operating formats can convey a persons commands to a computer. Future progress that moves from this demonstration stage to practical applications of long-term value to those with motor disabilities requires a flexible general purpose BCI system that can incorporate, compare, and (if indicated) combine these different methods, and can support generation of standard protocols for the clinical application of this new communication and control technology. The development and clinical validation of a general purpose BCI system is the goal of this Bioengineering Research Partnership (BRP) application. Each of the investigators in this partnership has been in the forefront of research into one of the current BCI methods, and together they have extensive experience in the development of BCI systems. The aims of this proposal are: (1) to develop a flexible general purpose BCI system that can incorporate any of the relevant signals, analyses, and operating formats and can be configured for laboratory or clinical needs; (2) to use the system to compare, contrast, and combine relevant brain signals and signal processing options during BCI operation and thereby develop a standard protocol for applying BCI technology to the needs of individual users; (3) to apply the system and protocol to address specific communication needs of people with severe motor disabilities and show that BCI technology is both useful to and actually used by these individuals;(4) to apply the system and protocol to develop the use of neuronal activity recorded within cortex for communication and control, and to define the relationships between this intracortical activity and scalp-recorded signals that might be used to guide or supplement invasive methods. Achievement of these aims and dissemination of the resulting technology to other research groups should advance BCI research from its current stage of laboratory demonstrations to development and validation of a general purpose BCI communication and control technology that can incorporate all relevant brain signals and has clear practical value for those with motor disabilities.